tbuckley/cabot-search huggingface dataset:
Cytokine profiles of peripheral blood in patients with non-small cell lung cancer receiving anti-PD1 therapy.
Authors: Maria A. Teplyakova, Liubov Yu Vladimirova, Irina L. Popova, Aza A. Lyanova, Natalia A. Abramova, Anna E. Storozhakova, Ludmila A. Ryadinskaya, Natalia M. Tikhanovskaya, Irina A. Udalenkova, Elena A. Kalabanova, Sergey N. Kabanov, Aleksandr B. Sagakyants, Elena Yu Zlatnik, Oksana G. Shulgina, Ekaterina I. Zolotareva, Elena P. Ulianova, Takhmina M. Kecheryukova, Marina M. Sergeeva, Yuriy N. Lazutin, Dmitry A. Kharagezov
Journal: Journal of Clinical Oncology (2022)

e21068 Background: Lung cancer (LC) is one of the most commonly diagnosed cancers and leading causes of cancer death worldwide. A limited clinical benefit of checkpoint inhibitor therapy (CIT) remains an important issue. Various units of the immune system are involved in both antitumor immunity and the development of CIT-induced side effects. Cytokines play a special role in these phenomena. The purpose of this study was to evaluate the cytokine profiles of peripheral blood in patients with non-small cell lung cancer (NSCLC) receiving CIT. Methods: The study included 32 NSCLC patients aged 41-83 years. CIT (pembrolizumab 2 mg/kg once every 21 days or 200 mg once every 21 days) continued until the appearance of reliable signs of the disease progression (in combination with symptomatic deterioration of the patient's condition). The effect was assessed by RECIST 1.1. The levels of cytokines (TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ) in the blood serum of patients were determined by ELISA before treatment, after 4 and after 8 injections. The results were expressed as specific content (units/mg). Results: The disease progression was registered in 14 patients, complete response in 7, partial response in 3 and stabilization in 8 patients. Only TNF-α was increased after CIT by 39% (11.3 [10.5; 15.4] vs. 8.1 [7.37;10.2] pg/mL, p≤0.037), while levels of IL-2, IL-4, IL-6 and IL-10 were lower than the initial values by 96%, 100%, 36% and 56%, respectively (0.06 [0.03; 0.45] vs. 1.65 [1.2;2.3], p≤0.034; 0 [0; 0.02] vs. 0.09 [0.05; 1.1], p≤0.031; 14.5 [8.5; 15.9] vs. 22.9 [18.1; 24.3], p≤0.042; 3.3 [2.7; 4.1] vs. 7.5 [6.4; 8.3] pg/mL, p≤0.038). No changes were found in the levels of IL-1β and IL-8 in the peripheral blood. Conclusions: Immunotherapy with pembrolizumab in the studied cohort of NSCLC patients after the 8th CIT cycle was characterized by a decline in the levels of cytokines (IL-2, IL-4, IL-6 and IL-10) determining the development of the cellular and humoral immune response, which may contribute to the treatment results.
Characteristics and information needs of patients with cancer contacting My Cancer Navigator (MCN): A personalized information service of the Anticancer Fund (ACF).
Authors: Gabry A.M. Kuijten, Nicolo Matteo Luca Battisti, Liese Vandeborne, Guy Buyens, Sergio Crispino
Journal: Journal of Clinical Oncology (2022)

e13521 Background: The ACF is an independent private research foundation, based in Belgium and active internationally. Since its inception in 2013, patients and their relatives spontaneously contact the Fund to request information on treatment options including clinical trials. MCN consists of a dedicated team of physicians and scientists, which provides patients and healthcare professionals with free, evidence-based, unbiased, and personalised information to support shared decision-making. All patients receive a summary report, which is discussed in a (video)call with one of our physicians. The objective of the current study was to analyse the characteristics and information requests of people contacting us in 2020-2021 in order to better understand their needs. Methods: For every information request through MCN, the patient agreed to the collection of anonymised data such as sex, age, geographic location and tumor type. We tracked questions asked in 8 categories, tracking a category only once per patient and including only those requiring a literature search. Only descriptive statistics were applied. Results: In 2020-2021, we received information requests for 511 unique patients: 483 adults (95%) and 28 children (5%). In 46% of the cases the patient established contact; for 51% it was a relative or friend, and in 3% the physician. 377 patients (73%) were from Europe, of whom 222 (43%) from Belgium, 56 (11%) from the UK and 23 (5%) from the Netherlands. 109 patients (21%) came from all other continents – of those, 60 (12%) were from the USA. Tumor diagnoses included: gastro-intestinal (114, 22%), breast (110, 22%), central nervous system (77, 15%), gynecological (36, 7%), hematologic (35, 7%), genito-urinary (29, 6%), with sarcomas, lung, head and neck, skin and unknown cancers making up the remainder. Most patients had more than 1 question requiring research, resulting in a total of 880 questions. The Table shows the number and percentage for each category. Conclusions: Within this population, evidence-based information on treatment options, clinical trials, complementary treatments and repurposed drugs were key information needs. Healthcare institutions may lack resources to address all information needs, and My Cancer Navigator may contribute to closing that gap and support patients and healthcare providers. Although the service seems to be well perceived, we are now developing a method to formally assess satisfaction with and impact of our service.[Table: see text]
Correlation of circulating tumor cells as a positive interventional biomarker in cancer patients.
Authors: Jayant Khandare, Gourishankar Aland, Sreeja Jayant, Pratim Chakraborti, Alain D'Souza, Avinash Kadam, Poonam Birari-Gawande, Yogesh Narayan Bendale
Journal: Journal of Clinical Oncology (2022)

e14527 Background: Circulating Tumor Cells (CTC) is a predictive biomarker for accounting disease progression and for minimal residual disease (MRD). Effect of conventional anticancer therapy on CTC count is well documented, however there is paucity of data related to effect of CAM based modality on CTC count in cancer patients. This study provides a preliminary observation about the effect of Ayurveda therapy on CTC count. Methods: The retrospective study involved stratification of 72 cancer patients undergoing cancer and maintenance treatment in a non-conventional, Ayurveda cancer treatment in India. For monitoring of prognosis in cancer patients, CTC count was assesed in patients attending Rasayu Cancer clinic. 17 cancer types, namely, breast cancer, cervix and ovarian cancer, bladder, lung, Head and neck squamous carcinoma, follicular thyroid, diffuse B-cell lymphoma, Hodgkin’s and non-Hodgkin’s, colorectal, Hepatocellular, stomach with abdominal metastasis, metastatic prostate cancer, SCC with lung and skeletal metastasis etc. Total 33 (46%) males and 39 (54.1%) female patients of various types and stages were analyzed for the presence of CTCs retrospectively. CTCs were isolated and renumerated from 1.5 ml of patient’s blood sample using OncoDiscover Liquid Biopsy Technology platform enriched with anti-EpCAM antibody immunomagnetic kit, approved by Drug Controller General of India (DCGI). CTCs were confirmed for cytokeratin + 18 (CK18), DAPI + and CD45 - . Subsequently CTCs were imaged using Zeiss Axio Observer 7 fluorescence microscope. In 28 patients (50%), CTC was accounted for at both pre and post treatment in duration of 3-6 months. 28 patients were assessed for quality of life measured by FACT-G questionnaire. The outcome was quantified for clinico-pathological parameters; age / gender, cancer types, and CTC distribution. Results: The mean and median CTC distribution was observed to be 15.34 and 12.5, respectively. 8% patients showed the absence of any CTCs (6 subjects (1 male and 5 females). While 32 males (96%) and 34 females (87%) showed presence of CTCs. The correlation coefficient of CTC presence in male and female was significant 0.4799 (p &lt; 0.05). The Ayurveda Rasayana therapy showed significant reduction in post interventional CTC count (-3.94±1.2) (P=0.02). In addition, this group of patients also showed significant improvement in health-related quality of life as measured by the FACT-G questionnaire (P&lt;0.05). Conclusions: CTC is a validated predictive biomarker for accounting minimal residual disease, both in pre and post cancer treatments. The enumeration of CTCs represents an effective prognostic biomarker in assessing the disease progression. Reduction in CTC count was seen to be associated with improvement in health-related quality of life (QoL) which needs to be investigated further to establish correlation.
Real-world (RW) treatment patterns and comparative effectiveness of Bruton tyrosine kinase inhibitors (BTKi) in patients (pts) with mantle cell lymphoma (MCL).
Authors: Bijal D. Shah, Keri Yang, Andrew J. Klink, Tom Liu, Todd M. Zimmerman, Ajeet Gajra, Boxiong Tang
Journal: Journal of Clinical Oncology (2022)

e18727 Background: BTKi therapies, approved for relapsed or refractory (R/R) MCL, have not been comprehensively evaluated in RW populations. This study aimed to assess patient characteristics, treatment patterns and associated outcomes in RW BTKi-treated MCL pts. Methods: The retrospective multicenter chart review was conducted in the Cardinal Health Oncology Provider Extended Network. EMR data were extracted for eligible pts diagnosed with MCL who initiated any of the approved BTKi (ibrutinib [ibr], acalabrutinib [acal], zanubrutinib [zanu]) from 2018 to 2021; pts enrolled in trials were excluded. Index date was defined as the use of any of the BTKis. Pts were followed 12-mo pre-index for medical history, and from index to last follow-up or death. Descriptive analyses were conducted to assess demographic/clinical characteristics, MCL baseline features, BTKi treatment patterns, adverse events (AE), and response rates by BTKi. Multivariable logistic regression was performed to assess factors associated with response and AE. Results: The study cohort consisted of 300 MCL pts (59% male; 69% white); most (64%) pts were covered by Medicare, 34% had commercial insurance. BTKis were given mainly as monotherapy (93%) and in R/R setting (86%). Pts in zanu group were significantly older (n = 100, median age = 71, range = 50-91) than pts in ibr (n = 100, median age = 69, range = 39-87) and acal (n = 100, median age = 70, range = 51-86) groups. Significantly fewer pts in the zanu group had baseline Ann Arbor stage I-II (4%) than ibr (10%) or acal (13%), while more zanu pts had presence of B symptoms (67%) than ibr (44%) or acal (57%). Pts in the zanu group also had significantly less with ECOG of 3+ (4%) compared to ibr (8%) or acal (6%). At BTKi initiation, significantly more pts in zanu group (18%) had history of atrial fibrillation than ibr (1%) or acal (5%). Multivariable regression reported a significant association of age, gender, extranodal/splenic involvement, and timing of BTKi initiation with response and AE (Table). Conclusions: This study provides the first RW evidence on comparative effectiveness of ibr, acal, zanu in MCL pts. While pts treated with zanu were older and had more complex MCL baseline features at initiation, multivariable regression suggested a trend favoring zanu over ibr or acal for both response and AE. Frontline initiation of BTKi therapy was also associated with improved tolerability. Future RW studies are needed to discern long-term outcomes.[Table: see text]
Correlation between PD-L1 high-expression and EGFR variants in non-small cell lung cancer.
Authors: Yifei Liu, Fei Quan, Siqi Chen, Guanghua Lu, Yuan Yang, Wanglong Deng, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2022)

e21062 Background: In previous studies, researchers have demonstrated that activation of the epidermal growth factor receptor (EGFR)-mutant pathway induced PD-L1 expression. In this study, we explored the correlation between PD-L1 expressions and EGFR variations. Methods: This study enrolled 2417 non-small cell lung cancer(NSCLC) patients harboring diverse EGFR mutations, including exon 19 deletions(19del)(n = 1045), L858R(n = 906), G719X(n = 176), S768I(n = 62), L861Q(n = 89) and exon 20 insertions(20ins)(n = 139). The stages range from I through IV, the majority were female(n = 1452, 60.07%) and adenocarcinoma(n = 1788, 73.98%), median age was 62(range 24-92). In this study, we retrospectively analyzed variants using next-generation sequencing(NGS). PD-L1 status was determined by VENTANA PD-L1 (SP263) Assay, TPS≥50% and TPS＜1% was the cut-off value for PD-L1 high-expression and negative separately. The 95% confidence interval (CI) was used to estimate the precision of the odds ratio (OR). Results: 1) Even though we observed subtle differences of PD-L1 high-expression ratio among various subtypes(19del：9.57%, L858R: 9.27%, G719X: 12.50%, S768I: 11.29%, L861Q: 7.87%, exon 20ins: 12.23%) in total patients, that PD-L1 high-expression was more likely to shown with G719X/S768I/exon 20ins than with 19del/L858R/L861Q, there was no statistically significant between 19del and other mutation：L858R(p = 0.8224), G719X (p = 0.2319), S768I(p = 0.6563), L861Q(p = 0.5982), exon 20ins(P = 0.3247). 2)We analyzed 742 treatment-naive EGFR-mutant NSCLC patients (PD-L1 negative, n = 624; high-expression, n = 118), PD-L1 high-expression group come with higher frequency of EGFR copy number variation(CNV)(OR = 2.2364, 95%CI, 1.4576-3.4312, p = 0.0002). Importantly, the ratio of high-level EGFR CNV(CN≥6) was higher in PD-L1 high-expression group than that in the negative group(OR = 3.0668, 95% CI, 1.3745-6.8427, p = 0.0062). Conclusions: In the newly diagnosed EGFR-mutant NSCLC patients, PD-L1 high-expression patients come with more frequent high-level EGFR CNV. There is no statistical significance between PD-L1 high-expression and EGFR mutation subtypes. As for how the EGFR signal affects PD-L1 expression, the mechanism needs to be further explored. The association between driver genes and immune checkpoints is a definite interest of future investigations.
Assessment of neurocognitive functions using ACE-III scale in patients with high-grade glioma receiving adjuvant chemoradiation.
Authors: Shreyosi Mandal, Deepa Joseph, Ajay S Krishnan, Pragya Singh, Rajnish Arora, Udit Chauhan, Sweety Gupta, Lekshmi R, Manoj Kumar Gupta
Journal: Journal of Clinical Oncology (2022)

e14030 Background: High Grade Gliomas (HGG) are aggressive CNS tumours with poor prognosis despite multimodality management with surgery, radiation and chemotherapy. During the course of the disease and treatment patients experience alterations in neurocognitive functions (NCF) &amp; QOL which is dependent on factors like size, location of tumour, type of surgery, chemo radiotherapy (CTRT) received &amp; disease recurrence. Assessment of change in pattern of NCF is important in optimising treatment and interventions like use of neuroprotectors and in guiding future clinical trials in those directions. Change in NCF significantly affects QOL of patients and their care givers. Most studies on NCF in brain tumours has been conducted on Low Grade Gliomas and various tools have been used in these studies. Addenbrooke Cognitive Examination tool (ACE III) has been used by some in the assessment of NCF in brain tumour. This study aims to assess change in NCF in postoperative HGG patients receiving adjuvant chemoradiation. Methods: 13 newly diagnosed post operative cases of Grade III &amp; IV gliomas were prospectively enrolled in the study. Enrolled patients received adjuvant radiotherapy (RT) (60Gy/30 fractions) using IMRT technique with concurrent Temozolomide (TMZ) 75mg/m2 over 6 weeks. Patients received adjuvant TMZ 150-200 mg/m2 up to six 4-weekly cycles. Pre-treatment Neurocognitive functions were assessed using ACE III scale before start of RT. Post-treatment assessment was done using ACE III at 6 months after completion of RT. The ACE-III scale consists of 5 domains namely Attention (Total Score-18), Memory (TS-26), Fluency (TS-14), Language (TS-26), Visuospatial Abilities (TS-16); the Total Score is given out of 100.The variable are described using mean (SD); Paired t test was used for statistical analysis and baseline data was compared with 6 months’ data. Results: The study group was homogenous with a median age of 42 years. Fronto-parietal region of the brain was most commonly involved. All patients had received concurrent TMZ, completed RT within 6 weeks and received adjuvant TMZ for a period of 6 months. On Comparing baseline to 6 months data; statistically significant improvement was noted in Memory(p-0.049), Language(p-0.031) &amp; the Total Score (p-0.048).There was improvement in total ACE III score in 84% of the patients at 6 months. Conclusions: Significant improvement noted in majority of the postoperative patients at 6 months’ post RT in both total ACE III score and specific domains except a few. Long term follow up needed to assess further change in NCF due to disease or long term treatment related effects.[Table: see text]
Independent validation of a novel noninvasive 4-microRNA diagnostic model for multicancer early detection.
Authors: Andrew Zhang, Hai Hu
Journal: Journal of Clinical Oncology (2022)

3065 Background: Cancer early detection is critical to reduce mortality as treating early stage cancers is more likely to have better outcomes. We previously developed a diagnostic model based on 4 serum cell-free microRNAs (miRNAs) capable of detecting 12 cancer types with high accuracy (AACR 2022, Poster 2890; Manuscript submitted). In the current study, we aimed to validate this diagnostic model using independent serum microRNA microarray datasets. Methods: Four microarray datasets assessing the expression of 2588 serum miRNAs in patients with esophageal squamous cell carcinoma, gastric cancer, prostate cancer and glioma, as well as non-cancer healthy controls with a standardized platform were identified from Gene Expression Omnibus (GEO). The datasets were combined, cases that were redundant among them or with the cases used in our previous study (correlation &gt; 0.99) were excluded. The 4-miRNA model was applied to the final combined dataset to calculate a diagnostic index and make prediction of cancer vs. no-cancer using previously determined algorithm and cut-point. The performance of the diagnostic model was assessed using Receiver Operating Characteristic (ROC) analysis, sensitivity and specificity. Results: After excluding redundant cases, the final combined dataset consisted of 3877 subjects, including 447 esophageal, 1267 gastric, 769 prostate and 196 glioma cancer patients, as well as 1198 healthy controls. The 4-miRNA model demonstrated an area under the curve (AUC) of 0.986, 0.995, 0.992 and 0.990 in the ROC analysis, with a sensitivity of 85.0%, 99.6%, 90.6% and 86.7% for esophageal, gastric, prostate and glioma cancers, respectively, while achieving a 99.1% specificity. These performance metrics were highly consistent to those reported in our previous study (Table). Conclusions: The study provided an independent validation of the previously developed 4-miRNA model, further demonstrating that the diagnostic model we developed has the potential to be developed into a simple, inexpensive and noninvasive blood test for multi-cancer early detection with high accuracy. [Table: see text]
Population kinetics assessment of limited small cell lung cancer (L-SCLC).
Authors: David J. Stewart
Journal: Journal of Clinical Oncology (2022)

e20602 Background: For most advanced malignancies, progression free survival (PFS) and overall survival (OS) curves approximate first order kinetics. 1 PFS and OS half-lives can be calculated by curve exponential decay nonlinear regression analysis (EDNLRA). Curve characteristics vary significantly with treatment and malignancy type. 1 On log-linear plots, PFS curves are significantly more likely to be convex for extensive SCLC than for other malignancies, with late acceleration of tumor growth after completion of 1 st line therapy. 1,2 Here we assess L-SCLC by EDNLRA. Methods: We used https://apps.automeris.io/wpd/ to digitize PFS curves from L-SCLC studies published from 1990 to 2021. We analyzed curves for study arms having &gt; 50 patients. We used GraphPad Prism 7 for 1 and 2 phase decay EDNLRA as previously described. 1 We also constructed log-linear plots. Results: We analyzed 55 L-SCLC PFS curves from 34 published trials. Median PFS half-life was 15 months for studies published 1990 to 2010 vs 19.5 months for 2011 to 2021 (P = 0.003). This improvement over time might be explained in part by stage migration (eg, with PET scanning). Of 55 log-linear plots, 53 (96%) had an inflection to the right. The curve inflection indicates there are 2 distinct subpopulations: namely progressing patients vs cured patients. Of the 55 curves, 46 fit 2 phase decay EDNLRA models. Across these 46 2-phase decay curves, EDNLRA calculations indicated that the progressing subgroup comprised 86% of the total population and had a PFS half-life of 10.5 months. The cured subgroup accounted for the other 14% of the population, with a PFS half-life greater than 15 years. The proportion cured increased from a median of 12% for 1990-2010 studies to 22% for 2011-2021 studies (p = 0.01). Stage migration might again explain this difference. For patients who are progression-free at any time point, one can also use these EDNLRA data to calculate the proportion who would eventually progress in the future. Of those still progression free at 12, 24, 36, 48, 60 and 120 months, respectively, the proportion that would eventually progress would be 73%, 56%, 36%, 20%, 10%, and 0.2%. As with extensive SCLC, all 55 L-SCLC PFS log-linear curves displayed early convexity, with a downward inflection after a period of relative stability. This downward inflection occurred at a median of 4.4 months, in keeping with acceleration of progression after completion of planned systemic therapy. Conclusions: Population kinetic assessments permit calculation of probability of eventual progression for L-SCLC patients who remain progression-free at different time points after initiation of therapy. Of L-SCLC patients who remain progression-free at 60 months, approximately 10% are nevertheless destined to eventually relapse. References: Stewart DJ et al. Crit Rev Oncol Hematol. 2020;153:103039. Stewart DJ et al. Proc American Soc Clin Oncol 2020. Abstract # e21101.